Without limiting the scope of the invention, its background is described in connection with K-ras and lung cancer.
The KRAS (Kirsten-ras) oncogene is mutated in a significant proportion of pancreatic ductal adenocarcinoma (PDAC), colorectal and non-small-cell lung cancers (NSCLC). In the majority of PDAC (70-90%) patients carrying KRAS mutations, the five-year survival rate is less than 5%. KRAS is a member of guanine nucleotide-binding protein family and is an integral component of multiple intracellular signaling pathways including epidermal growth factor receptor (EGFR). The overwhelming majority of mutations in KRAS are single nucleotide somatic mutations resulting in single amino acid substitutions at codons 12 or 13. The G12D, G12V, G12R and G12C KRAS mutations comprise >90% of KRAS mutations found in PADC patients. KRAS mutations essentially result in constitutively active KRAS and unregulated downstream signaling.
Targeted agents such as the antibody Cetuximab (in colorectal cancer) and the small molecular inhibitor vemurafenib (in BRAF mutant melanoma), perform poorly in patients with KRAS mutations. Consequently an effective cancer therapeutic strategy requires KRAS mutation selectivity sparing wild-type functionality. There remains a great need for compositions, methods and treatments for cancers with KRAS mutations.
U.S. Pat. No. 7,893,034, issued to Slack, et al., is entitled “Regulation of oncogenes by microRNAs.” Briefly, these inventors describe targeting naturally occurring miRNAs that regulate human oncogenes and methods of use thereof. Suitable nucleic acids for use in the methods and compositions described by the inventors are said to include, but not be limited to, pri-miRNA, pre-miRNA, mature miRNA or fragments of variants thereof that retain the biological activity of the mature miRNA and DNA encoding a pri-miRNA, pre-miRNA, mature miRNA, fragments or variants thereof, or regulatory elements of the miRNA. The inventors also discuss compositions containing nucleic acids are administered to a patient in need of treatment or prophylaxis of at least one symptom or manifestation of cancer. In one specific embodiment, the compositions are said to be administered in an effective amount to inhibit gene expression of one or more oncogenes. Methods for treatment or prevention of at least one symptom or manifestation of cancer are also described.